Background : Topical therapy with comedolytics and antibiotics are often advocated for mild and moderate severity acne vulgaris. Nadifloxacin, a new fluoroquinolone with anti-Propionibacterium acnes activity and additional anti-inflammatory activity, is approved for use in acne. This randomized controlled assessor blind trial compared the clinical effectiveness and safety of eight weeks therapy of nadifloxacin 1% versus clindamycin 1% as add-on therapy to benzoyl peroxide (2.5%) in mild to moderate grade acne.
Materials and Methods : The efficacy parameters were changes in the total, inflammatory and non-inflammatory lesion counts, Investigator Global Assessment (IGA), and Cardiff Acne Disability Index (CADI) scales from baseline to study end (eight weeks). All treatment emergent dermatological adverse events were evaluated for safety assessment.
Results : Out of 84 randomized subjects (43-nadifloxacin arm) and (41-clindamycin) 42 in nadifloxacin group, 37 in clindamycin group completed the study. Reduction from baseline of total, inflammatory and non-inflammatory lesion counts were highly significant in both the groups (P<0.0001), but between group differences were not significant. Significant improvement in CADI and IGA scales were noted in both groups. Between-group comparison showed no significant differences. The safety and tolerability profile of both regimens were good and statistically comparable.
Conclusions: Topical nadifloxacin, a new fluoroquinolone is effective, tolerable, and safe for mild o moderate facial acne. Its clinical effectiveness is comparable to clindamycin when used as add-on therapy to benzoyl peroxide.

Potential of nonantibiotic therapies for treatment of Helicobacter pylori-related acid peptic disease remains underexplored. Several clinical studies have shown that higher prevalence of H. pylori infection is associated with low Vitamin C (Vit C) level in serum and gastric juice. However, there is no consensus regarding the usefulness of Vit C supplementation in the management of H. pylori infection. Surveying the existing literature we conclude that high concentration of Vit C in gastric juice might inactivate H. pylori urease, the key enzyme for the pathogen's survival and colonization into acidic stomach. Once infection established, urease is not very important for its survival. The role of Vit-C as anti-H. pylori agent in peptic ulcer diseases appears to be preventive rather than curative. Rather than supplementing high dose of Vit C along with conventional triple therapy, it is preferable to complete the conventional therapy and thereafter start Vit C supplementation for extended period which would prevent reinfection in susceptible individuals, provided the patients are not achlorhydric. Further studies are required to prove the role of Vit C in susceptible population.

Aim : The effect of monotherapy with racemic salbutamol and levosalbutamol on symptoms, quality of life, and pulmonary function has been assessed and compared in mild persistent asthma.
Materials and Methods : A randomized, open, parallel clinical study was conducted on 60 patients of mild persistent asthma. After baseline assessments, salbutamol was prescribed to 30 patients and levosalbutamol to another 30 for 4 weeks. The efficacy variables were change in asthma symptom scoring, pulmonary function test, and Mini Asthma Quality of Life Questionnaire (MiniAQLQ) scoring. At follow-up, the patients were re-evaluated and analyzed by statistical tools.
Results : Shortness of breath (P<0.001), chest tightness (P=0.033), wheeze (P=0.01), cough (P=0.024), and overall asthma symptom score (P<0.001) were significantly decreased in the levosalbutamol group in comparison to the salbutamol group. Results of MiniAQLQ revealed that improvement in symptoms (P=0.018), activity limitations (P=0.03), environmental stimuli (P=0.013)-related scoring and overall MiniAQLQ scoring (P<0.001) was statistically significant in the levosalbutamol group. Percentage reversibility of forced expiratory volume at one second (P=0.034), forced vital capacity (P=0.029), peak expiratory flow rate (P=0.0003) was found to be superior in the levosalbutamol group.
Conclusion : Levosalbutamol was found to be superior compared to recemic salbutamol in mild persistent asthma.

Objective : To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation
Materials and Methods : The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40 mg/kg, p.o were tested.
Results : The fraction FRI (40 mg/kg, p.o.) and FRIII (40 mg/kg, p.o) were found to be more effective (P<0.01) in preventing carrageenan induced rat paw edema, cotton pellet granuloma formation, and acetic acid induced writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20 mg/kg, p.o.) were also found to be more effective in increasing latency period in tail flick method.
Conclusion : Out of five different fractions of F. religiosa leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory activities against different models of inflammation and pain.

Objective : This study was undertaken to evaluate the neuroprotective activity of Wedelia calendulacea against cerebral ischemia/reperfusion induced oxidative stress in the rats.
Materials and Methods : The global cerebral ischemia was induced in male albino Wistar rats by occluding the bilateral carotid arteries for 30 min followed by 1 h and 4 h reperfusion. At various times of reperfusion, the histopathological changes and the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST), and hydrogen peroxide (H 2 O 2 ) activity and brain water content were measured.
Results : The ischemic changes were preceded by increase in concentration of MDA, hydrogen peroxide and followed by decreased GPx, GR, and GST activity. Treatment with W. calendulacea significantly attenuated ischemia-induced oxidative stress. W. calendulacea administration markedly reversed and restored to near normal level in the groups pre-treated with methanolic extract (250 and 500 mg/kg, given orally in single and double dose/day for 10 days) in dose-dependent way. Similarly, W. calendulacea reversed the brain water content in the ischemia reperfusion animals. The neurodegenaration also conformed by the histopathological changes in the cerebral-ischemic animals.
Conclusion : The findings from the present investigation reveal that W. calendulacea protects neurons from global cerebral-ischemic injury in rat by attenuating oxidative stress.

Objective : The aim of the present study was to evaluate the sedative and antiepileptic activities of ethanolic extract of Anthocephalus cadamba (ACE) bark in various experimental animal models.
Materials and Methods : ACE was tested at three doses viz. 100, 200 and 400 mg/kg p.o. We used ketamine-induced sleeping time model to test the sedative property of the extract where, onset and duration of sleep were observed. A paradigm of anticonvulsant models (pentylenetetrazole, isoniazid and maximal electroshock-induced seizures) were used to evaluate its protective effect against absence and generalized types of seizures. Onset of clonic convulsions, tonic extension and time of death were observed in PTZ and INH-induced seizure models. In MES model, duration of tonic hind leg extension and onset of stupor were observed.
Results : ACE showed significant increase in ketamine induced sleeping time. It also exhibited significant increase (P<0.05, 0.01 and 0.001) in latency to clonic convulsion, tonic extension and time of death in PTZ and INH models at all tested doses, whereas in the MES model, the lower dose was found to be effective when compared with the higher doses (200 and 400 mg/kg, p.o.).
Conclusion : The results of the present investigation demonstrated that ACE possesses sedative and antiepileptic activities.

The main aim of treatment of early rheumatoid arthritis (RA) should be to achieve clinical remission to prevent structural damage and physical disability. Arthrofoon modifies production/activity of endogenous inhibitors of tumor necrosis factor-α (TNF-α). The sublingual rout is the most acceptable to ambulatory treatment because it does not produce the adverse reactions associated with intravenous therapy. The treatment with arthrofoon in outpatient with early RA is analyzed here. This report is devoted to the 28-year-old Russian woman who received arthrofoon due to suspicion of early RA. The strategy of early prescription of ultra-low doses of TNF-α antibody within two years was confirmed by the clinical improvement and delay of radiological disease progression in patient with undifferentiated arthritis or probable RA initially.

Objective : To investigate standardized ethyl acetate fraction of Rhododendron arboreum (EFRA) flowers for antidiarrheal activity in experimental animals.
Materials and Methods : A simple sensitive high performance thin layer chromatography (HPTLC) method was used for the determination of hyperin in EFRA. The standardized fraction was investigated for castor oil, magnesium sulfate-induced diarrhea, measurement of gastrointestinal transit using charcoal and castor oil-induced enteropooling.
Results : The concentration of hyperin in flowers of R. arboreum was found to be 0.148% by HPTLC. Oral administration of EFRA at 100, 200 and 400 mg/kg exhibited dose-dependent and significant (P<0.05-0.001) antidiarrheal potential in castor oil and magnesium sulfate-induced diarrhea. EFRA at doses of 100, 200 and 400 mg/kg also produced significant (P<0.05-0.001) dose-dependent reduction in propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in rats. EFRA was found to possess an antienteropooling in castor oil-induced experimental animals by reducing both weight and volume of intestinal content significantly.
Conclusion : These findings demonstrate that standardized ethyl acetate fraction of R. arboreum flowers has potent antidiarrheal activity thus justifying its traditional use in diarrhea and have great potential as a source for natural health products.

Objective : Human experimental pain models help to understand the mechanism of the painful conditions and can also be adopted to test analgesic efficacy of drugs. In early phases, the clinical development of new analgesics is hindered due to the lack of reliable tests for the experimental pain models. In the present study, we have developed and validated a simple radiant heat pain model which can be used for future screening of various analgesic agents.
Materials and Methods : We have standardized the thermal pain model by recording pain threshold and pain tolerance time in seconds at three different intensities and levels in 24 healthy subjects. Reproducibility of the test procedure was evaluated by recording the pain parameters by two observers on three consecutive days. Validity of model was further tested by evaluating the analgesic effect of tramadol.
Results and Conclusions : Use of radiant heat pain model with high intensity and short level was found to produce low variability with coefficient of variation less than 5%. Interobserver and interperiod reproducibility was very good as shown by Bland - Altman plot; with most of the values within ± 2SD. Tramadol produced statistically significant increase in pain threshold time. The newly developed pain model produces a type of experimental pain which is responsive to analgesic effects of tramadol at clinically relevant doses.

Objectives and Aim : This study was designed to analyze the relationship between the expression of c-Fos protein and apoptosis in the hippocampus following propofol administration in infant mice. There are reports that certain drugs, including the general anesthetics applied in pediatrics and obstetrics, could block N-methyl-D-aspartate glutamate receptors and activate γ-aminobutyric acid type A receptors. Furthermore, some anesthetics could trigger neuroapoptosis and the expression of c-Fos in the developing rodent brain. Propofol is a general anesthetic increasingly used in pediatrics and obstetrics, and is reported to be able to interact with both γ-aminobutyric acid type A and N-methyl-D-aspartate glutamate receptors. No adequate evaluations have been available as to whether the dosage of propofol to maintain anaesthesia could trigger the expression of c-Fos and apoptosis.
Materials and Methods : Intraperitoneal injections of propofol (50, 100 and 150 mg/kg) or vehicle were administered every 90 minutes (4 times) in infant mice (5-7 days old). 30 minutes after the final administration, the protein expressions of c-Fos and cleaved-caspase-3 in the hippocampus were determined by immunohistochemistry and Western blotting.
Results : It was demonstrated that the expressions of cleaved-caspase-3 and c-Fos were upregulated in the hippocampal CA3 region in this study.
Conclusions : The upregulated c-Fos expression induced by repeated injections of propofol might evoke neuroapoptosis.

Objective : The present study was aimed to investigate the diuretic effects of aqueous (AqE) and ethanolic (EtE) crude extracts of Hemidesmus indicus R. Br. roots (family - Asclepiadaceae) using acute model in rats.
Materials and Methods : A single individual dose of AqE and EtE of H. indicus root (200 mg/kg and 400 mg/kg, p.o., each), frusemide and hydrochlorothiazide, (25 mg/kg, p.o., each) as reference diuretic drugs were administered orally to dehydrated rats. Control group rats were fed with normal saline (25 ml/kg, p.o.). All rats were caged in metabolic cages in a pairs and their urine output was monitored at 5 and 24 h intervals.
Results : Both extracts significantly increased the urine output in higher doses. Although, the onset of this diuretic action was gradual (within 5 h), it lasted throughout the studied period (up to 24 h). Further, the intensity of diuresis induced by AqE (400 mg/kg) in 5 h was almost similar to that of frusemide and hydrochlothiazide. AqE of H. indicus root also caused marked increase in urinary Na + and K + levels. However, the routine urinalysis showed non-significant alterations in pH and specific gravity by either dose of crude extracts of H. indicus roots.
Conclusions : These effects demonstrate possible diuretic actions of H. indicus root extracts and support its folklore use in various urinary ailments. Further study need to be done to characterize active phytoconstituents.

The Z-category hypnotics are promoted for their relative safety. However, this view is challenged by the emerging clinical evidence in the form of zolpidem related intoxication delirium and seizures, and dependence and complicated withdrawal. We report the case of a zolpidem-naive alcohol-dependent inpatient that, while undergoing alcohol de-addiction, was prescribed zolpidem for insomnia and developed delirium during taper-off. He was successfully detoxified for alcohol, treated for delirium and put on disulfiram prophylaxis. The case highlights the need for being cautious while using zolpidem for insomnia in alcohol dependent subjects.

Objective : Ischemia/reperfusion (I/R) injury plays a key role in the pathogenesis of hepatic failure in several clinical settings such as liver resection or transplantation. Lisinopril, a widely prescribed drug for various cardiovascular conditions, has been reported to have diverse pharmacological properties. The aim of this study, therefore, was to evaluate a potential protective effect of lisinopril on hepatic I/R injury in rats.
Materials and Methods : In anesthetized rats, partial hepatic ischemia was applied for one hour followed by two hours reperfusion. Biochemical analysis of serum and hepatic tissue was done. Hepatic tissue was also subjected to electron microscopy.
Results : Pre-ischemic treatment with lisinopril (10 mg/kg) exerted protection against I/R-induced hepatocellular injury as evident by significant decrease in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels, along with hepatic lipid peroxidation, expressed as malondialdehyde content, with a concurrent increase in hepatic nitric oxide content as compared to I/R group. The electron microscopic examination indicated that lisinopril can effectively protect against hepatic I/R injury.
Conclusion : Lisinopril provides a protection against hepatic I/R injury in rats. The protective effect is associated with reduction of oxidative stress-induced lipid peroxidation level and enhancement of nitric oxide availability.

We report a case of cholestatic hepatitis developed one week after exposure to azathioprine. The subsequent prolonged cholestatic phase was followed by full clinical remission. Current knowledge on pathogenesis and epidemiology and the diagnostic challenges presented by this rare complication are discussed, followed by recommendations for monitoring and management.

Background and Purpose : Voltage dependent anion channel (VDAC) plays an important role in triggering the opening of the mitochondrial permeability transition pore (PTP) that leads to mitochondrial damage and induce apoptic or necrotic cell death. In the present study, the methanolic extract of Amomum subulatum Roxb. seeds (MEAS) was used to examine its effect on VDAC. Aminotransferase activity, mitochondrial membrane potential, calcium-induced liver MPT, and VDAC expression were used to evaluate the hepato protective effect of MEAS.
Results : Pretreatment of mice with MEAS (100 and 300 mg/kg) significantly blocked the CCl 4 -induced increase in AST and ALT activities. Pretreatment with MEAS showed significant preservation of mitochondrial membrane potential as compared to CCl 4 control demonstrating the mitochondrial protection. In addition, pretreatment with MEAS at various concentrations exerted a dose-dependent effect against sensitivity to mitochondrial swelling induced by calcium. In addition, MEAS (300 mg/kg) significantly increased the transcription and translation of VDAC.
Conclusion : Our data suggest that MEAS significantly prevents the damage to liver mitochondria through regulation of VDAC expression.

A 3-year-old female patient developed chorea possibly due to an interaction between phenytoin, phenobarbital and clobazam used for generalized tonic clonic seizures. Phenytoin withdrawal resulted in recovery within 24 hours. Post reaction computerized tomography (CT)-scan of brain was normal. Combined use of anti-seizure drugs and interactions between them may be responsible for the reaction. Therapeutic drug monitoring is important while prescribing two or more anti-seizure drugs.

The treatment of baclofen overdose is primarily supportive. There have been case reports of hemodialysis being used in patients with chronic kidney disease with baclofen overdose. A case report of hemodialysis in a baclofen-overdose patient with normal renal function is presented. Review of literature has also been provided.

Objective : To compare the efficacy and safety profile of dalteparin, a low-molecular-weight heparin with a standard unfractionated heparin in patients with unstable angina pectoris.
Materials and Methods : This was a 6-month, prospective, parallel, randomized and open-labeled study. Patients of angina pectoris were randomized to receive either unfractionated heparin or dalteparin for 5 days. They were followed for 21 days during three visits on 1 st , 5 th and 21 st days. A series of resting electrocardiogram were undertaken in all patients on each visit.
Results : The frequency of the combined clinical outcome of death, myocardial infarction and recurrence of angina was similar during 21 days of follow-up with either dalteparin or intravenous unfractionated heparin. In patients who received dalteparin 2.43% patients developed minor bleeding in the form of epistaxis and 2.5% patients who received unfractionated heparin developed minor bleeding in the form of macroscopic hematuria.
Conclusion : Dalteparin is as effective and safe as unfractionated heparin in the treatment of unstable angina. Dalteparin does not require routine laboratory monitoring as with unfractionated heparin.

Objective : To assess the renoprotective activity of the water extract of Annona squamosa in 5/6 nephrectomized animals.
Materials and Methods : For evaluating the renoprotective effects of Annona squamosa, 5/6 nephrectomized rats were used as a model for renal failure. The effects of hot-water extract of leaves of Annona squamosa L. (A. squamosa) at a dose 300 mg/kg bw on biochemical and urinary parameters like plasma urea, plasma creatinine, and urine creatinine were analyzed. For elucidating its effect on oxidative stress, renal superoxide dismutase (SOD) levels were measured.
Results : Nephrectomized rats (5/6) showed a significant rise in plasma urea and creatinine levels with a stable fall in urine creatinine. Treatment with A. squamosa extract (300 mg/kg bw) lead to a significant fall in the plasma urea and creatinine values with partial restoration to normal values along with a significant rise in the activity of SOD.
Conclusion : Thus, therapeutic strategies against oxidative stress could be effective in renal diseases. This study provides an indication to investigate further the efficacy of A. squamosa as a novel agent for alleviating renal failure.

Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy.

Objective : The in vivo and in vitro antitumor activity of kaurenic acid [kaur 16-en-19 oic acid] (KA) in melanoma was evaluated in a murine model in comparison with taxol (Tx).
Materials and Methods : B16F1 melanoma was developed in C57BL/6 mice and cell cultures. Survival test, tumor growth, dissected-tumor measurements, histology, cytoxicity assay on cultured cells, and changes of apoptotic gene expression at mRNA level were analyzed.
Results : KA showed antitumor effect in vivo and in vitro and compared with Tx, its antimelanoma activity was greater (P < 0.001). These results were confirmed by morphological analysis (P < 0.001). In melanoma cell cultures, KA IC 50 was 0.79 μM vs. 18.94 μM for Tx (P < 0.001). RT-PCR analysis demonstrated that Bcl-xL mRNA expression was altered in B16F1 mouse melanoma cells obtained from mice treated with either KA or Tx.
Conclusion : The data suggest that KA is active in animal melanoma models, both in vitro and in vivo, being its cytotoxic effects stronger than those exhibited by Tx. Further trials should be conducted to elucidate its mechanism of action in melanoma with respect to necrosis or apoptotic processes. Our results support other evidences indicating that KA is a potential chemotherapeutic agent against cancer that has to be widely explored.

A 44-year-old man presented with acute coronary syndrome. He was administered glycoprotein IIb/IIIa receptor antagonist (tirofiban) for a left anterior descending artery thrombus detected during percutaneous coronary intervention. He developed very severe thrombocytopenia 24 h after tirofiban infusion with no signs of bleeding. The thrombocytopenia spontaneously resolved after stopping tirofiban without any significant clinical sequelae. To our knowledge, this is the first case report of tirofiban-induced severe thrombocytopenia from the Middle East. Clinicians using this drug should be aware of this potentially lethal adverse drug reaction. Close monitoring of platelet count early after the initiation of tirofiban infusion is suggested and discontinuation of tirofiban infusion can reverse thrombocytopenia spontaneously.

Objective : To evaluate the ability of acute or chronic treatment with fluoxetine to alter the proerectile effect of Aspidosperma ulei alkaloid-rich fraction (F3-5).
Materials and Methods : In the first series of experiments, three groups of mice received either a single intraperitoneal injection of vehicle, F3-5 (25 mg/kg) or fluoxetine (10 mg/kg) + F3-5. Three behavioral responses were counted over a period of 30 min: erection, erection-like response and genital grooming. In a second series of experiments, animals treated for 13 days with fluoxetine or fluoxetine + F3-5 were assessed.
Results : A. ulei has been suggested to have proerectile effect in mice. Subchronic (13-d) treatment with fluoxetine resulted in a reduction in the number erections in F3-5-treated mice.
Conclusion : Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapy. Acute administration of fluoxetine resulted in a near total reversal of the proerectile effect of F3-5.